Sökning: onr:"swepub:oai:DiVA.org:umu-64160" >
Ca2+ enhances Aβ po...
Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner
-
- Brännström, Kristoffer (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Anders Olofsson
-
- Öhman, Anders (författare)
- Umeå universitet,Klinisk neurovetenskap
-
- Lindhagen-Persson, Malin (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
visa fler...
-
- Olofsson, Anders (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
visa färre...
-
(creator_code:org_t)
- Portland Press, 2013
- 2013
- Engelska.
-
Ingår i: Biochemical Journal. - : Portland Press. - 0264-6021 .- 1470-8728. ; 450, s. 189-197
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Identifying factors that affect the self-assembly of the amyloid-β peptide (Aβ) is of utmost importance in the quest to understand the molecular mechanisms causing Alzheimer's disease (AD). Ca2+ has previously been shown to accelerate both Aβ fibril nucleation and maturation, and a dysregulated Ca2+ homeostasis frequently correlates with development of AD. The mechanisms regarding Ca2+ binding as well as its effect on fibril kinetics are not fully understood. Using a polymerization assay we show that Ca2+ in a dynamic and reversible manner enhances both the elongation rate and fibrillar stability, where specifically the "dock and lock" phase mechanism is enhanced. Through NMR analysis we found that Ca2+ affects the fibrillar architecture. In addition, and unexpectedly, we found that Ca2+ does not bind the free Aβ monomer. This implies that Ca2+ binding requires an architecture adopted by assembled peptides, and consequently is mediated through intermolecular interactions between adjacent peptides. This gives a mechanistic explanation to the enhancing effect on fibril maturation and indicates structural similarities between prefibrillar structures and mature amyloid. Taken together we expose how Ca2+ levels affect the delicate equilibrium between the monomeric and assembled Aβ and how fluctuations in vivo may contribute to development and progression of the disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- amyloid
- amyloid-beta peptide (A beta)
- atomic force microscopy (AFM)
- Ca2
- NMR
- surface plasmon resonance (SPR)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas